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25-11-2021 | Multiple myeloma | Adis Journal Club | Article

Clinical Drug Investigation

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician’s Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

Authors: Katja Weisel, Thomas Martin, Amrita Krishnan, Sundar Jagannath, Anil Londhe, Sandhya Nair, Joris Diels, Martin Vogel, Jordan M. Schecter, Arnob Banerjee, Jesus G. Berdeja, Tonia Nesheiwat, Ashraf Garrett, Keqin Qi, Satish Valluri, Saad Z. Usmani & Kwee Yong

Abstract

Background and Objective

Ciltacabtagene autoleucel (cilta-cel) is a novel agent being investigated in the single-arm CARTITUDE-1 trial (NCT03548207) for patients with relapsed or refractory multiple myeloma who are triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody. The objective of this study was to evaluate the comparative efficacy of cilta-cel vs physician’s choice of treatment, as no head-to-head trials have been conducted.

Methods

An external control arm for CARTITUDE-1 was created from patients in the long-term follow-up for three clinical trials of daratumumab (POLLUX, CASTOR, and EQUULEUS) who satisfied the eligibility criteria of CARTITUDE-1. These patients received physician’s choice of treatment following the discontinuation of study drugs. Inverse probability of treatment weighting was used to align the external control and CARTITUDE-1 populations on important baseline characteristics. Overall response rate, complete response or better rate, progression-free survival, time to next treatment, and overall survival were assessed. Several sensitivity analyses were conducted.

Results

After propensity score weighting, baseline characteristics were comparable between cohorts. Patients showed improved results with cilta-cel vs physician’s choice of treatment: overall response rate (relative risk: 2.95 [95% confidence interval (CI) 2.27, 3.84; p < 0.0001]), complete response or better (relative risk: 111.70 [95% CI 29.08, 429.06; p < 0.0001]), progression-free survival (hazard ratio [HR]: 0.24 [95% CI 0.15, 0.37; p < 0.0001]), time to next treatment (HR: 0.14 [95% CI 0.09, 0.22; p < 0.0001]), and overall survival (HR: 0.21 [95% CI 0.13, 0.35; p < 0.0001]). Results were consistent across all sensitivity analyses.

Conclusions

Cilta-cel showed superior efficacy compared with physician’s choice of treatment, making it a promising new treatment option for patients with triple-class exposed relapsed or refractory multiple myeloma.

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 Key Points

Ciltacabtagene autoleucel (cilta-cel; CARTITUDE-1) and physician’s choice of treatment (post-trial data for three daratumumab clinical trials, POLLUX, CASTOR, and EQUULEUS) were indirectly compared given the absence of direct head-to-head trials.

Cilta-cel demonstrated statistically and clinically superior efficacy results compared to physician’s choice of treatment. Based on these findings, cilta-cel offers substantial clinical benefits for patients with triple-class exposed relapsed or refractory multiple myeloma.

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